Bottom Line:
Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI).The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI.These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant.

ABSTRACTDetection of immunoreactants including IgG, IgM, IgA, and C3 by direct immunofluorescence (DIF) from skin is useful for distinguishing lupus lesions from other skin disorders. Despite their diagnostic value, the type and number of cutaneous immunoreactants as they relate to serological disorders and disease severity has been poorly studied. We examined 36 patients with systemic lupus erythematosis (SLE) with positive DIF (DIF+) and 28 patients with negative DIF (DIF-) tests performed on lesional skin. Among DIF+ patients, the most frequent patterns of immunoreactants were IgM alone (36%) and the coexistence of IgM with C3 (28%). IgM was the highest detected individual immunoreactant (86%). As classified by number, 17 of 36 DIF+ patients had one immunoreactant (= 1), while the remaining patients had two to four immunoreactants (>1). Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI). The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI. These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant. Collectively, the presence of multiple immunoreactants in lesional skin implies a more severe disease activity of SLE, while a single immunoreactant may be equal to the absence of immunoreactants (DIF-) in terms of predicting disease activity.

pone-0070983-g003: The comparison of serum C3 concentration and SLEDAI in groups of patients Patients were first divided into DIF− and DIF+ groups.DIF+ group was then divided into two subgroups according to the existence pattern (A, B) and the number of immunoreactants(C, D), respectively. Serum C3(A, C) and SLEDAI(B,D) were compared among each of four groups. Each symbol represents one individual, and the bar indicates the mean. Statistical analysis was performed with one-way analysis of variance followed by Dunn’s post hoc test for three groups. *P<0.05, ** P<0.01.

Mentions:
Second, because IgM was the most frequent immunoreactant, we determined whether cutaneous IgM deposits are associated with serological disorders. DIF+ patients were divided into three subgroups according to the pattern of cutaneous IgM (number of patients): IgM alone (13), IgM+ other immunoreactant (18), and IgM negative and DIF positive (IgM-DIF+) (5). The subsequent analysis focused on the first two subgroups because only five patients were IgM- DIF+. The presence of SLE-related antibodies including ANA, dsDNA, SSA, RNP, and Sm did not differ among the IgM-alone, IgM+other immunoreactants, and DIF− groups (P>0.05). Interestingly, none of the 18 patients with IgM+other immunoreactants in the skin showed SSB-positive serum samples, whereas 7 SSB-positive serum samples were detected from the other groups (2 of 28 DIF− patients, 1 of 5 IgM-DIF+ patients, and 4 of 13 IgM alone patients) (Table 2). The serum level of C3 in the group of patients with cutaneous IgM+other immunoreactants (359±148, mean ± SD) was lower than that in the DIF− group (580±232), but comparable with that in the IgM-alone group (538±222), whereas there were no statistically significant differences between the latter two groups (Figure 3A, Table 2). These results suggest that the pattern of cutaneous IgM along with other immunoreactants is related to a higher disease activity. This was further confirmed by SLEDAI analysis. The SLEDAI of 18 patients with cutaneous IgM+other immunoreactants was 9.6±3.7 (mean ± SD), higher than that in the DIF− group (6.8±3.9) but comparable with the IgM-alone group (6.8±3.9); the latter two groups showed no statistical significance (P>0.05) (Figure 3B, Table 2). Comparisons among these groups were also performed in terms of the complete blood cell count and ESR, and revealed no association with the pattern of cutaneous IgM (data not shown).

pone-0070983-g003: The comparison of serum C3 concentration and SLEDAI in groups of patients Patients were first divided into DIF− and DIF+ groups.DIF+ group was then divided into two subgroups according to the existence pattern (A, B) and the number of immunoreactants(C, D), respectively. Serum C3(A, C) and SLEDAI(B,D) were compared among each of four groups. Each symbol represents one individual, and the bar indicates the mean. Statistical analysis was performed with one-way analysis of variance followed by Dunn’s post hoc test for three groups. *P<0.05, ** P<0.01.

Mentions:
Second, because IgM was the most frequent immunoreactant, we determined whether cutaneous IgM deposits are associated with serological disorders. DIF+ patients were divided into three subgroups according to the pattern of cutaneous IgM (number of patients): IgM alone (13), IgM+ other immunoreactant (18), and IgM negative and DIF positive (IgM-DIF+) (5). The subsequent analysis focused on the first two subgroups because only five patients were IgM- DIF+. The presence of SLE-related antibodies including ANA, dsDNA, SSA, RNP, and Sm did not differ among the IgM-alone, IgM+other immunoreactants, and DIF− groups (P>0.05). Interestingly, none of the 18 patients with IgM+other immunoreactants in the skin showed SSB-positive serum samples, whereas 7 SSB-positive serum samples were detected from the other groups (2 of 28 DIF− patients, 1 of 5 IgM-DIF+ patients, and 4 of 13 IgM alone patients) (Table 2). The serum level of C3 in the group of patients with cutaneous IgM+other immunoreactants (359±148, mean ± SD) was lower than that in the DIF− group (580±232), but comparable with that in the IgM-alone group (538±222), whereas there were no statistically significant differences between the latter two groups (Figure 3A, Table 2). These results suggest that the pattern of cutaneous IgM along with other immunoreactants is related to a higher disease activity. This was further confirmed by SLEDAI analysis. The SLEDAI of 18 patients with cutaneous IgM+other immunoreactants was 9.6±3.7 (mean ± SD), higher than that in the DIF− group (6.8±3.9) but comparable with the IgM-alone group (6.8±3.9); the latter two groups showed no statistical significance (P>0.05) (Figure 3B, Table 2). Comparisons among these groups were also performed in terms of the complete blood cell count and ESR, and revealed no association with the pattern of cutaneous IgM (data not shown).

Bottom Line:
Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI).The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI.These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant.

ABSTRACTDetection of immunoreactants including IgG, IgM, IgA, and C3 by direct immunofluorescence (DIF) from skin is useful for distinguishing lupus lesions from other skin disorders. Despite their diagnostic value, the type and number of cutaneous immunoreactants as they relate to serological disorders and disease severity has been poorly studied. We examined 36 patients with systemic lupus erythematosis (SLE) with positive DIF (DIF+) and 28 patients with negative DIF (DIF-) tests performed on lesional skin. Among DIF+ patients, the most frequent patterns of immunoreactants were IgM alone (36%) and the coexistence of IgM with C3 (28%). IgM was the highest detected individual immunoreactant (86%). As classified by number, 17 of 36 DIF+ patients had one immunoreactant (= 1), while the remaining patients had two to four immunoreactants (>1). Compared with DIF- patients, DIF+ patients were more likely to have severe disease as indicated by lower serum C3 levels and a higher SLE disease activity index (SLEDAI). The coexistence of IgM with any other immunoreactants indicated a more severe disease than that present in the DIF- group, whereas the IgM-alone group was comparable with the DIF- group in both serum C3 levels and SLEDAI. These findings were also applicable in the comparison of patients with more than one (>1) immunoreactant and patients with no (DIF-) and one ( = 1) immunoreactant. Collectively, the presence of multiple immunoreactants in lesional skin implies a more severe disease activity of SLE, while a single immunoreactant may be equal to the absence of immunoreactants (DIF-) in terms of predicting disease activity.